(a) Field of the Invention
The invention relates to DNA-based immunization technology for the vaccination of animals against BVDV.
(b) Description of Prior Art
Bovine viral diarrhea virus (BVDV), an economically important pathogen of cattle, is an enveloped single-stranded RNA virus classified as a member of the genus Pestivirus within the Flaviviridae family. The BVDV genome is approximately 12.5 kb in length and contains one large open reading frame (ORF). The ORF codes for a large polyprotein of approximately 450 kDa which is processed co- and post-translationally by either host and viral proteases. The N-terminal end of standard BVDV polyprotein results in a non-structural protein p20 (Npro), capsid protein p14 (C); envelope glycoproteins gp48 (E0), gp25 (E1), gp53 (E2); non-structural proteins p125 (NS23), p10 (NS4A), p32 (NS4B), p58 (NS5A) and p75 (NS5B). BVDV may exist in two biotypes, cytopathic or non-cytopathic. The two biotypes differ by the production of an 80 kDa polypeptide (non-structural protein p80, NS3) by the cytopathic BVDV. Recently, based on the antigenic and genomic studies, subgroups of BVDV appear to represent two different genotype (1 and 2).
BVDV, like other RNA viruses such as influenza, are known for their high antigenic variation. These BVDV variants that evolve through immune selective pressure may lead to the incomplete protection often observed after conventional vaccination. This antigenic diversity raises the challenge to always includes in the next vaccine, the new antigenic BVDV variant. This antigenic variability of BVDV strains has created the demand for a new generation of vaccines.
A number of monoclonal antibodies directed against the BVDV major glycoprotein gp53 (E2) have been shown to possess virus-neutralizing activity.
Direct injection of DNA into animals is a novel and promising technology for delivering specific antigens for immunization. This approach has recently been shown to induce both humoral and cellular immune responses against several infectious agents, such as influenza, rabies, human immunodeficiency, bovine herpes viruses, and malaria.
However, it would be highly desirable to be provided with a plasmidic expression vector having the immunogenic potential of the BVDV genotype 1 gp53 (E2) protein or another BVDV immunogenic protein when injected into mice without presenting the drawbacks of the conventional vaccination.